DOCSLIB.ORG

NDUFAB1 Confers Cardio-Protection by Enhancing Mitochondrial Bioenergetics Through Coordination of Respiratory Complex and Supercomplex Assembly

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
NDUFAB1 Confers Cardio-Protection by Enhancing Mitochondrial Bioenergetics Through Coordination of Respiratory Complex and Supercomplex Assembly www.nature.com/cr www.cell-research.com ARTICLE OPEN NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly Tingting Hou1, Rufeng Zhang1, Chongshu Jian1, Wanqiu Ding1, Yanru Wang1, Shukuan Ling2,QiMa1, Xinli Hu1, Heping Cheng1 and Xianhua Wang1 The impairment of mitochondrial bioenergetics, often coupled with exaggerated reactive oxygen species (ROS) production, is a fundamental disease mechanism in organs with a high demand for energy, including the heart. Building a more robust and safer cellular powerhouse holds the promise for protecting these organs in stressful conditions. Here, we demonstrate that NADH: ubiquinone oxidoreductase subunit AB1 (NDUFAB1), also known as mitochondrial acyl carrier protein, acts as a powerful cardio- protector by conferring greater capacity and efficiency of mitochondrial energy metabolism. In particular, NDUFAB1 not only serves as a complex I subunit, but also coordinates the assembly of respiratory complexes I, II, and III, and supercomplexes, through regulating iron-sulfur biosynthesis and complex I subunit stability. Cardiac-specific deletion of Ndufab1 in mice caused defective bioenergetics and elevated ROS levels, leading to progressive dilated cardiomyopathy and eventual heart failure and sudden death. Overexpression of Ndufab1 effectively enhanced mitochondrial bioenergetics while limiting ROS production and protected the heart against ischemia-reperfusion injury. Together, our findings identify that NDUFAB1 is a crucial regulator of mitochondrial energy and ROS metabolism through coordinating the assembly of respiratory complexes and supercomplexes, and thus provide a potential therapeutic target for the prevention and treatment of heart failure. Cell Research (2019) 29:754–766; https://doi.org/10.1038/s41422-019-0208-x INTRODUCTION sites in the complexes from oxidative damage, and stabilize Being so-called “powerhouses”, mitochondria comprise up to 40% individual complexes.11,15–21 Interestingly, SC formation is dyna- of the heart mass and are central to cardiac bioenergetics.1,2 As mically regulated in accordance with changes in cellular hazardous by-products of energy metabolism, reactive oxygen metabolism,22–25 and deficiency of SCs is associated with heart species (ROS) are also emitted from the respiratory electron failure.26 Therefore, enhancing SC formation might afford an transport chain (ETC), and excessive ROS emission causes effective therapeutic strategy to make the mitochondria more oxidative damage to proteins, lipids, and even genetic materials.3,4 efficient and safer powerhouses. Studies have shown that >50% of individuals with mutations in NADH:ubiquinone oxidoreductase subunit AB1 (NDUFAB1), also genes encoding mitochondrial proteins eventually develop known as mitochondrial acyl carrier protein,27 plays a multi- cardiomyopathy,5 suggesting that defective cardiac bioenergetics functional role in the organelle. It not only participates in the as well as its interlinked ROS metabolism is a fundamental disease synthesis of lipoic acid in the type II fatty acid biosynthetic mechanism in the heart.6,7 As such, building a more robust cellular pathway (FAS II),28,29 but also acts as an accessory subunit of powerhouse with decreased ROS emission holds the promise for complex I with a 2:1 stoichiometry.30 A recent study has shown protecting the heart in stressful conditions. that NDUFAB1 interacts with seven mitochondrial LYR motif- The most important player in mitochondrial energy production containing (LYRM) proteins: LYRM1, LYRM2, LYRM4/ISD11, LYRM5, is the ETC, which consists of four multi-heteromeric complexes LYRM7/MZM1L, SDHAF3/ACN9, and FMC1/C7orf55.31 Most of (complexes I–IV) in the inner membrane of the organelle. They them are linked to various mitochondrial metabolic processes, catalyze outward proton movement to build a transmembrane such as the assembly of complex II (for SDHAF3/ACN9) and electrochemical gradient that drives ATP synthase (complex V) for complex V (for FMC1/C7orf55), deflavination of the electron- ATP synthesis.8 Individual ETC complexes can also organize into transferring flavoprotein (for LYRM5), and biosynthesis of iron- supercomplexes (SCs) of different composition and stoichiometry, sulfur (FeS) centers (for LYRM4/ISD11).31 In yeast cells which lack which have recently been visualized by cryo-electron micro- complex I, Van et al. have shown that NDUFAB1 interacts with and scopy.9–14 Such SCs are thought to channel electron transfer stabilizes the FeS biogenesis complex to regulate the assembly of more efficiently, limit ROS production, protect vulnerable ETC complexes II and III and SCs.32 In addition, previous evidence in 1State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing 100871, China and 2State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China Correspondence: Heping Cheng ([email protected]) or Xianhua Wang ([email protected]) Received: 16 January 2019 Accepted: 2 July 2019 Published online: 31 July 2019 © The Author(s) 2019 Article 755 293T cells has also suggested a role of NDUFAB1 in complex I and the inter-ventricular septum was decreased whereas the left assembly and the existence of a complex I-independent mechan- ventricular diameter and volume were increased with age in cKO ism for Ndufab1 knockout-induced cell death.33 Thus, NDUFAB1 hearts (Supplementary information, Fig. S2b, c). These findings might be a core player in orchestrating mitochondrial energy indicate that cardiac-specific ablation of NDUFAB1 leads to dilated biogenesis. cardiomyopathy accompanied by cardiomyocyte hypertrophy, In this study, we aimed to test the potential protective role of interstitial fibrosis, and systolic and diastolic dysfunction, even- NDUFAB1 in the mammalian heart using cardiac-specific Ndufab1 tually resulting in heart failure and sudden death, revealing an knockout (cKO) and transgenic overexpression (TG) mouse essential role of NDUFAB1 in cardiac function. models. We find that NDUFAB1 coordinates the assembly of individual ETC complexes and SCs and acts as a crucial Mitochondrial dysfunctions in Ndufab1 cKO heart endogenous regulator of the efficiency and capacity of mitochon- To investigate the mechanism underlying the cardiomyopathy drial energy metabolism as well as ROS emission. More and heart failure induced by NDUFAB1 ablation, we next assessed importantly, NDUFAB1 exerts a cardio-protective effect when the changes of cardiac mitochondrial functions at different ages of heart is subjected to ischemia-reperfusion (IR) injury. Our findings cKO mice. Electron microscopic analysis revealed that cardiac substantiate that targeting mitochondria for greater bioenergetic mitochondria were in disarray along the sarcomeres with some capacity and repressed ROS emission with enhanced SC formation exhibiting irregularities in the cristae formation in 16-week-old is an effective strategy for cardio-protection, and mark NDUFAB1 cKO mice, whereas mitochondrial morphology was apparently as a potential therapeutic target for the prevention and treatment normal at 6 weeks, when the cardiac function hadn’t been of cardiomyopathy. impaired yet (Fig. 2a). The mitochondrial DNA content and cross- sectional area of individual mitochondria didn’t display detectable changes whereas the total mitochondrial volume fraction and RESULTS mitochondrial number were slightly increased in 16-week-old cKO Cardiac-specific ablation of NDUFAB1 causes progressive dilated mice (Supplementary information, Fig. S3). Measuring mitochon- cardiomyopathy leading to heart failure drial membrane potential (ΔΨm) in isolated cardiomyocytes with NDUFAB1 was widely expressed in different tissues and was the potential-sensitive fluorescent probe tetramethyl rhodamine particularly enriched in the heart (Supplementary information, methyl ester (TMRM) showed that NDUFAB1 ablation significantly Fig. S1a). Whole-body knockout of Ndufab1 was embryonic lethal decreased ΔΨm even at 6 weeks (Fig. 2b) when the heart 1234567890();,: (Supplementary information, Fig. S1b, c), showing that NDUFAB1 morphology and function were normal (Fig. 1), indicating is essential for developmental viability. To explore the potential mitochondrial dysfunction is an early event in cKO mice preceding cardiac functions of NDUFAB1, we generated a cardiac-specific the onset of cardiomyopathy. Measurements with the fluorescent knockout mouse model (cKO) wherein exon 3 of Ndufab1 was probe mitoSOX showed that mitochondrial ROS level was flanked by loxP sites (Ndufab1flox/flox, Supplementary information, significantly elevated in cKO cardiomyocytes compared to WT at Fig. S1b). The Ndufab1flox/flox mice were cross-bred with Mlc2v-Cre 10 weeks, and increased by 72% at 14–16 weeks, reaching a level mice to allow cardiomyocyte-specific deletion of Ndufab1,as comparable to that induced by 5 μg/mL antimycin A (Fig. 2c). The previously described.34 As shown in Fig. 1a and Supplementary cellular ATP level, as measured with the luciferin luminescence information, Fig. S1d, cardiac expression of Ndufab1 was assay, showed a trend of decrease in cKO mice from 6 to 8 weeks decreased by ~90% at the protein level in cKO cardiomyocytes old and was significantly lowered in 14–16-week or older cKO compared to wild-type (WT) cells. The
Load more

Recommended publications
  • DNA Breakpoint Assay Reveals a Majority of Gross Duplications Occur in Tandem Reducing VUS Classifications in Breast Cancer Predisposition Genes
    © American College of Medical Genetics and Genomics ARTICLE Corrected: Correction DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes Marcy E. Richardson, PhD1, Hansook Chong, PhD1, Wenbo Mu, MS1, Blair R. Conner, MS1, Vickie Hsuan, MS1, Sara Willett, MS1, Stephanie Lam, MS1, Pei Tsai, CGMBS, MB (ASCP)1, Tina Pesaran, MS, CGC1, Adam C. Chamberlin, PhD1, Min-Sun Park, PhD1, Phillip Gray, PhD1, Rachid Karam, MD, PhD1 and Aaron Elliott, PhD1 Purpose: Gross duplications are ambiguous in terms of clinical cohort, while the remainder have unknown tandem status. Among interpretation due to the limitations of the detection methods that the tandem gross duplications that were eligible for reclassification, cannot infer their context, namely, whether they occur in tandem or 95% of them were upgraded to pathogenic. are duplicated and inserted elsewhere in the genome. We Conclusion: DBA is a novel, high-throughput, NGS-based method investigated the proportion of gross duplications occurring in that informs the tandem status, and thereby the classification of, tandem in breast cancer predisposition genes with the intent of gross duplications. This method revealed that most gross duplica- informing their classifications. tions in the investigated genes occurred in tandem and resulted in a Methods: The DNA breakpoint assay (DBA) is a custom, paired- pathogenic classification, which helps to secure the necessary end, next-generation sequencing (NGS) method designed to treatment options for their carriers. capture and detect deep-intronic DNA breakpoints in gross duplications in BRCA1, BRCA2, ATM, CDH1, PALB2, and CHEK2. Genetics in Medicine (2019) 21:683–693; https://doi.org/10.1038/s41436- Results: DBA allowed us to ascertain breakpoints for 44 unique 018-0092-7 gross duplications from 147 probands.
    [Show full text]
  • Autism Multiplex Family with 16P11.2P12.2 Microduplication Syndrome in Monozygotic Twins and Distal 16P11.2 Deletion in Their Brother
    European Journal of Human Genetics (2012) 20, 540–546 & 2012 Macmillan Publishers Limited All rights reserved 1018-4813/12 www.nature.com/ejhg ARTICLE Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother Anne-Claude Tabet1,2,3,4, Marion Pilorge2,3,4, Richard Delorme5,6,Fre´de´rique Amsellem5,6, Jean-Marc Pinard7, Marion Leboyer6,8,9, Alain Verloes10, Brigitte Benzacken1,11,12 and Catalina Betancur*,2,3,4 The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5–30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5–30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28–30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40–29.25 Mb), inherited from his apparently healthy father.
    [Show full text]
  • Mouse Ndufab1 Knockout Project (CRISPR/Cas9)
    https://www.alphaknockout.com Mouse Ndufab1 Knockout Project (CRISPR/Cas9) Objective: To create a Ndufab1 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Ndufab1 gene (NCBI Reference Sequence: NM_028177 ; Ensembl: ENSMUSG00000030869 ) is located on Mouse chromosome 7. 5 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 4 (Transcript: ENSMUST00000033157). Exon 2~4 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 2 starts from about 36.11% of the coding region. Exon 2~4 covers 64.1% of the coding region. The size of effective KO region: ~5146 bp. The KO region does not have any other known gene. Page 1 of 9 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 2 3 4 5 Legends Exon of mouse Ndufab1 Knockout region Page 2 of 9 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 2 is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section downstream of Exon 4 is aligned with itself to determine if there are tandem repeats.
    [Show full text]
  • Mechanistic Insights Into GLUT1 Activation and Clustering Revealed by Super-Resolution Imaging
    Mechanistic insights into GLUT1 activation and clustering revealed by super-resolution imaging Qiuyan Yana,b, Yanting Lub,c, Lulu Zhoua,b, Junling Chena, Haijiao Xua, Mingjun Caia, Yan Shia, Junguang Jianga, Wenyong Xiongc,1, Jing Gaoa,1, and Hongda Wanga,d,1 aState Key Laboratory of Electroanalytical Chemistry, Research Center of Biomembranomics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 Jilin, P. R. China; bSchool of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, 100049 Beijing, P. R. China; cState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201 Yunnan, P. R. China; and dLaboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Aoshanwei, Jimo, Qingdao, 266237 Shandong, P. R. China Edited by Nieng Yan, Princeton University, Princeton, NJ, and accepted by Editorial Board Member Alan R. Fersht May 24, 2018 (received for review March 9, 2018) The glucose transporter GLUT1, a plasma membrane protein that super-resolution fluorescence microscopy, which breaks the dif- mediates glucose homeostasis in mammalian cells, is responsible fraction barrier and achieves a lateral resolution in the tens of for constitutive uptake of glucose into many tissues and organs. nanometers (17), has provided a particularly suitable tool to solve Many studies have focused on its vital physiological functions and these problems. Meanwhile, it has been proven that multiprotein close relationship with diseases. However, the molecular mecha- assemblies are dependent on cholesterol environment, and their nisms of its activation and transport are not clear, and its detailed separation and anchoring are related to the actin cytoskeleton (18, distribution pattern on cell membranes also remains unknown.
    [Show full text]
  • NDUFAB1 Protects Heart by Coordinating Mitochondrial Respiratory Complex
    bioRxiv preprint doi: https://doi.org/10.1101/302281; this version posted April 16, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. NDUFAB1 Protects Heart by Coordinating Mitochondrial Respiratory Complex and Supercomplex Assembly Running title: Hou et al. Cardiac Protection by NDUFAB1 Tingting Hou 1; Rufeng Zhang 1; Chongshu Jian 1; Wanqiu Ding 1; Yanru Wang 1; Qi Ma 1; Xinli Hu 1; Heping Cheng 1,†; Xianhua Wang 1,† 1State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, China. † Corresponding author. Xianhua Wang Tel: 86-10-62754605 Email: [email protected] Heping Cheng Tel: 86-10-62765957 Email: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/302281; this version posted April 16, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The impairment of mitochondrial bioenergetics, often coupled with exaggerated reactive oxygen species (ROS) production, is emerging as a common mechanism in diseases of organs with a high demand for energy, such as the heart. Building a more robust cellular powerhouse holds promise for protecting these organs in stressful conditions. Here, we demonstrate that NDUFAB1 (NADH:ubiquinone oxidoreductase subunit AB1), acts as a powerful cardio-protector by enhancing mitochondrial energy biogenesis. In particular, NDUFAB1 coordinates the assembly of respiratory complexes I, II, and III and supercomplexes, conferring greater capacity and efficiency of mitochondrial energy metabolism.
    [Show full text]
  • Anti-NDUFAB1 Monoclonal Antibody, Clone FQS7836 (DCABH-6999) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Anti-NDUFAB1 monoclonal antibody, clone FQS7836 (DCABH-6999) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Rabbit monoclonal to NDUFAB1 Antigen Description Carrier of the growing fatty acid chain in fatty acid biosynthesis in mitochondria. Accessory and non-catalytic subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. Immunogen Synthetic peptide (the amino acid sequence is considered to be commercially sensitive) within Human NDUFAB1 aa 100 to the C-terminus. The exact sequence is proprietary.Database link: O14561 Isotype IgG Source/Host Rabbit Species Reactivity Mouse, Human Clone FQS7836 Purity Tissue culture supernatant Conjugate Unconjugated Applications IP, Flow Cyt, IHC-P, WB Positive Control Molt-4, A431 and HepG2 cell lysate. Human heart and kidney tissue. HepG2 cells. Format Liquid Size 100 μl Buffer Preservative: 0.01% Sodium azide; Constituents: 40% Glycerol, 59% PBS, 0.05% BSA Preservative 0.01% Sodium Azide Storage Store at +4°C short term (1-2 weeks). Upon delivery aliquot. Store at -20°C long term. Avoid freeze / thaw cycle. Ship Shipped at 4°C. 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved GENE INFORMATION Gene Name NDUFAB1 NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1, 8kDa [ Homo sapiens ] Official Symbol NDUFAB1
    [Show full text]
  • NDUFAB1 Rabbit Polyclonal Antibody – TA308227 | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA308227 NDUFAB1 Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IF, IHC, WB Recommended Dilution: ICC/IF:1:100-1:1000; IHC:1:100-1:1000; WB:1:1000-1:10000 Reactivity: Human (Predicted: Bovine, Chimpanzee, Rhesus Monkey, X. tropicalis, Xenopus, Pig) Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: Synthetic peptide corresponding to a region within amino acids 93 and 156 of NDUFAB1 (Uniprot ID#O14561) Formulation: 0.1M Tris, 0.1M Glycine, 10% Glycerol (pH7). 0.01% Thimerosal was added as a preservative. Concentration: lot specific Purification: Purified by antigen-affinity chromatography. Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 17 kDa Gene Name: NADH:ubiquinone oxidoreductase subunit AB1 Database Link: NP_004994 Entrez Gene 4706 Human O14561 Synonyms: ACP; FASN2A; SDAP Note: Seq homology of immunogen across species: Xenopus laevis (100%), Xenopus Tropicalis (100%), Pig (100%), Rhesus Monkey (100%), Chimpanzee (100%), Bovine (100%) Protein Pathways: Alzheimer's disease, Huntington's disease, Metabolic pathways, Oxidative phosphorylation, Parkinson's disease This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 NDUFAB1 Rabbit Polyclonal Antibody – TA308227 Product images: NDUFAB1 antibody detects NDUFAB1 protein by Western blot analysis. A. 30 ug GL261 whole cell lysate/extract.
    [Show full text]
  • A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins
    membranes Review A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins Takahiko Aoki Laboratory of Quality in Marine Products, Graduate School of Bioresources, Mie University, 1577 Kurima Machiya-cho, Mie, Tsu 514-8507, Japan; [email protected]; Tel.: +81-59-231-9569; Fax: +81-59-231-9557 Received: 18 August 2017; Accepted: 24 September 2017; Published: 29 September 2017 Abstract: Human red blood cells (RBC), which are the cells most commonly used in the study of biological membranes, have some glycoproteins in their cell membrane. These membrane proteins are band 3 and glycophorins A–D, and some substoichiometric glycoproteins (e.g., CD44, CD47, Lu, Kell, Duffy). The oligosaccharide that band 3 contains has one N-linked oligosaccharide, and glycophorins possess mostly O-linked oligosaccharides. The end of the O-linked oligosaccharide is linked to sialic acid. In humans, this sialic acid is N-acetylneuraminic acid (NeuAc). Another sialic acid, N-glycolylneuraminic acid (NeuGc) is present in red blood cells of non-human origin. While the biological function of band 3 is well known as an anion exchanger, it has been suggested that the oligosaccharide of band 3 does not affect the anion transport function. Although band 3 has been studied in detail, the physiological functions of glycophorins remain unclear. This review mainly describes the sialo-oligosaccharide structures of band 3 and glycophorins, followed by a discussion of the physiological functions that have been reported in the literature to date. Moreover, other glycoproteins in red blood cell membranes of non-human origin are described, and the physiological function of glycophorin in carp red blood cell membranes is discussed with respect to its bacteriostatic activity.
    [Show full text]
  • Gene Section Review
    Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Review PALB2 (partner and localizer of BRCA2) Helmut Hanenberg and Paul R. Andreassen Department of Pediatrics III, University Children's Hospital Essen, University Duisburg-Essen, Essen Germany; [email protected] (HH); Division of Experimental Hematology & Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati OH, USA; [email protected] (APR) Published in Atlas Database: April 2018 Online updated version : http://AtlasGeneticsOncology.org/Genes/PALB2ID46402ch16p12.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/69016/04-2018-PALB2ID46402ch16p12.pdf DOI: 10.4267/2042/69016 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2018 Atlas of Genetics and Cytogenetics in Oncology and Haematology called FANCN and FANCD1, both characterized by Abstract severe congenital abnormalities and very early onset PALB2 (Partner and Localizer of BRCA2) was first of various cancers. This includes acute leukemias, identified as a BRCA2-interacting protein. Wilms tumor, medulloblastoma and Subsequently, PALB2 has been recognized as a cog neuroblastomas. Also, heterozygous germ-line in the cellular machinery for DNA repair by mutations of PALB2, like mutations in several other homologous recombination (HR). PALB2 also essential HR genes listed above, yield an increased mediates S and G2 DNA damage checkpoints, and susceptibility to breast and pancreatic cancer. has an apparent function in protecting Keywords transcriptionally active genes from genotoxic stress. Fanconi anemia; Breast Cancer Susceptibility; PALB2 also interacts with, is localized by, and Tumor Suppressor; Homologous Recombination; functions downstream of BRCA1.
    [Show full text]
  • Time Dependent Pathway Activation of Signalling Cascades in Rat Organs After Short-Term Hyperoxia
    International Journal of Molecular Sciences Article Time Dependent Pathway Activation of Signalling Cascades in Rat Organs after Short-Term Hyperoxia Jochen Hinkelbein 1,*,†, Stefan Braunecker 2,† ID , Matthias Danz 3, Lennert Böhm 4 and Andreas Hohn 1 1 Department of Anesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937 Cologne, Germany; [email protected] 2 Department of Anaesthesiology, St George’s University Hospital, NHS Foundation Trust, London SW17 0QT, UK; [email protected] 3 Department of Anesthesiology, St. Martinus Hospital, 57462 Olpe, Germany; [email protected] 4 Emergency Department, University of Duesseldorf, 40225 Düsseldorf, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-221-478-82042 † These authors contributed equally to this work. Received: 1 May 2018; Accepted: 29 June 2018; Published: 4 July 2018 Abstract: Administration of oxygen is one of the most common interventions in medicine. Previous research showed that differential regulated proteins could be linked to hyperoxia-associated signaling cascades in different tissues. However, it still remains unclear which signaling pathways are activated by hyperoxia. The present study analyses hyperoxia-induced protein alterations in lung, brain, and kidney tissue using a proteomic and bioinformatic approach. Pooled data of 36 Wistar rats exposed to hyperoxia were used. To identify possible hyperoxia biomarkers, and to evaluate the relationship between protein alterations in hyperoxia affected organs and blood, proteomics data from brain, lung, and kidney were analyzed. Functional network analyses (IPA®, PathwaysStudio®, and GENEmania®) in combination with hierarchical cluster analysis (Perseus®) was used to identify relevant pathways and key proteins. Data of 54 2D-gels with more than 2500 significantly regulated spots per gel were collected.
    [Show full text]
  • NDUFAB1 Antibody (C-Term) Affinity Purified Rabbit Polyclonal Antibody (Pab) Catalog # Ap14139b
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 NDUFAB1 Antibody (C-term) Affinity Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP14139b Specification NDUFAB1 Antibody (C-term) - Product Information Application WB, IHC-P,E Primary Accession O14561 Other Accession Q9CR21, P52505, NP_004994.1 Reactivity Human Predicted Bovine, Mouse Host Rabbit Clonality Polyclonal Isotype Rabbit IgG Antigen Region 128-156 NDUFAB1 Antibody (C-term) - Additional Information NDUFAB1 Antibody (C-term) (Cat. #AP14139b) western blot analysis in Gene ID 4706 MDA-MB435 cell line lysates (35ug/lane).This demonstrates the NDUFAB1 antibody Other Names detected the NDUFAB1 protein (arrow). Acyl carrier protein, mitochondrial, ACP, CI-SDAP, NADH-ubiquinone oxidoreductase 96 kDa subunit, NDUFAB1 Target/Specificity This NDUFAB1 antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 128-156 amino acids from the C-terminal region of human NDUFAB1. Dilution WB~~1:1000 IHC-P~~1:10~50 Format Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is purified through a protein A NDUFAB1 (C-term) column, followed by peptide affinity (AP14139b)immunohistochemistry analysis in purification. formalin fixed and paraffin embedded human kidney tissue followed by peroxidase Storage conjugation of the secondary antibody and Maintain refrigerated at 2-8°C for up to 2 DAB staining.This data demonstrates the use weeks. For long term storage store at -20°C of NDUFAB1 (C-term) for in small aliquots to prevent freeze-thaw immunohistochemistry. Clinical relevance has cycles. not been evaluated. Page 1/2 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Precautions NDUFAB1 Antibody (C-term) is for research use only and not for use in diagnostic or NDUFAB1 Antibody (C-term) - Background therapeutic procedures.
    [Show full text]
  • GLUT-1 Content and Interaction with Stomatin in Red Blood Cells from Species Without Vitamin C Biosynthesis and Their Relevance for Diabetes Mellitus Type 1
    GLUT-1 content and interaction with stomatin in red blood cells from species without vitamin C biosynthesis and their relevance for diabetes mellitus type 1 Dissertation zur Erlangung eines Doktorgrades der Naturwissenschaften ( Dr. rer. nat. ) Fakultät Naturwissenschaften Universität Hohenheim Institut für biologische Chemie und Ernährungswissenschaften vorgelegt von Tabea Caroline Frey aus Freiburg im Breisgau 2016 Dekan: Prof. Dr. Heinz Breer Erstgutachter: Prof. Dr. Hans Konrad Biesalski Zweitgutachter: Prof. Dr. Jan Frank Eingereicht am: 22.04.2016 Mündliche Prüfung: 28.07.2016 Die vorliegende Arbeit wurde am 27.06.2016 von der Fakultät Naturwissenschaften der Universität Hohenheim als 'Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften' angenommen. Abstract Ascorbic acid is commonly known as vitamin C. By denition, vitamins, with the exception of vitamin D, are substances which can not be synthesized but are essential for the organism. In this light vitamin C is special. It is hypothesized that millions of years ago some species, like primates, guinea pigs and fruit bats, lost the ability to synthesize ascorbate from glucose due to an inactivation of an enzyme called L-gulono-g-lactone oxidase. Since then, these species have been dependent on dietary intake of this micronutrient. Ascorbate is not only the most ecient watersoluble antioxidant, but also an important cofactor in neuro-transmitter or collagen biosynthesis. An inadequate intake of this vitamin leads to scurvy. In 2008, a French researcher documented that all species that lost the ability to synthesize ascorbic acid express a dierent facilitative glucose transporter isoform (GLUT) in their erythrocytes. The expressed GLUT-1 transports not only glucose but also dehydroascorbate which is the oxidized form of vitamin C.
    [Show full text]